Studies are in progress which focus on enzymic and local vasoactive mediator factors in tumor tissue that may influence vascular aspects of the tumor and its growth. Two protease pre-enzymes (neutral and acid proteases) have been isolated from tumor tissue which, when activated, were found capable of forming potent vasopeptides from specific tumor and plasma substrates. Purification of the acid protease has been achieved using gel adsorption and filtration techniques. These include Bio-Gel A-5M, hydroxylapatite, and DEAE-cellulose (DE-52). Relative to initial tumor tissue enzyme activity, an approximate 10,000-fold purification has been accomplished. Tumor kininogen substrate also was purified, and the vasopeptides isolated following incubation of enzyme and substrate. The acid protease activity can be preserved or restored with mercaptoethanol, and inactivated irreversibly by iodoacetic acid. The above suggests the possible involvement of sulfhydryl group(s) of the enzyme molecule for enzyme activity. Studies with synthetic inhibitors reveal that kinin-forming activity of the enzyme is inhibited by compounds containing hydrophobic, carboxyl, and either C equals O or OH groups. An acid protease from fibroblasts capable of forming kinins also has been purified. The kinetic actions of the enzyme, pH profile, and molecular weight have been studied as well as the subcellular localization.